LaVoieHealthScience Client Spotlight with Dror Bashan, CEO of Protalix BioTherapeutics
Can you provide a brief overview of Protalix BioTherapeutics and its focus?
Protalix BioTherapeutics is a unique biopharmaceutical company dedicated to bringing to market recombinant therapeutic proteins with clinically improved profiles, produced with our ProCellEx® plant cell-based expression.
Protalix was the first company ever to gain FDA approval for a recombinant therapeutic protein derived from a plant-cell culture expression system. Today, we are developing proprietary, potentially clinically superior versions of recombinant therapeutic proteins that target established pharmaceutical markets and patient populations.
We recently submitted a Biologics License Application (BLA) to the U.S. FDA for our lead compound, PRX-102, for the treatment of Fabry disease, through the FDA’s Accelerated Approval pathway.
Our initial commercial focus has been on complex therapeutic proteins, including proteins for the treatment of rare genetic disorders, such as Gaucher disease and Fabry disease. We believe that our ProCellEx® protein expression system gives us the ability to develop new and proprietary recombinant proteins that are potentially therapeutically superior to existing recombinant proteins currently marketed for the same indications.
In 2009, we collaborated with Pfizer for the development and commercialization of Elelyso® (taliglucerase alfa) an enzyme replacement therapy for the long-term treatment of adult and pediatric patients with a confirmed diagnosis of type 1 Gaucher disease.
Our vision is to become a fully integrated biopharmaceutical company leveraging the advantages of our unique technology platform and internal research and development capabilities.
What is unique about your manufacturing platform and what benefits does it bring to the drug development process?
Our pioneering ProCellEx® protein expression system is a plant cell based recombinant protein production system based on advanced genetic engineering and plant cell culture technology.
Over the years, Protalix has proven this technology to be a highly effective alternative to the mammalian cell-based production technology, which is the most common form of recombinant protein production. ProCellEx® overcomes many of the weaknesses of conventional recombinant protein production while offering significant production, regulatory, and cost benefits.
As opposed to mammalian cells, plant cells can tolerate a relatively wide range of culturing conditions and naturally do not carry the risk of infection by human or animal pathogens. This translates into lower capital investment in the set up as well as in ongoing maintenance of the production plant. Plant cells can use a simple culture medium with no requirement to any animal originated supplements.
In the ProCellEx® process, cell growth, from scale up through large-scale production, takes place in flexible, sterile, polyethylene bioreactors, situated in a clean-room environment. The reactors are custom-designed and optimized for plant cell cultures and are rapidly scalable horizontally.
This platform can offer a number of significant opportunities for biopharmaceutical manufacturing. In particular, ProCellEx® has a very broad range of expression capabilities. This technology is uniquely able to produce a broad array of complex glycosylated proteins, some of which are difficult to produce in mammalian, bacterial and yeast cell-based systems. And through this technology, it is possible in certain cases to develop and commercialize recombinant proteins without infringing upon the method-based patents or other intellectual property rights of third parties.
Describe your pipeline for therapeutic proteins.
We are advancing clinical programs addressing Fabry disease, cystic fibrosis, and inflammatory diseases. All our pipeline candidates are proteins expressed via our ProCellEx® system. In addition, Protalix is conducting initial research to evaluate additional programs for developing proprietary proteins with improved clinical profiles exploiting the unique nature of plant cell expression.
Our primary program, pegunigalsidase alfa or PRX-102 is being developed to treat Fabry disease, an X-linked inherited disease that results from abnormal deposits of a fatty substance called globotriaosylceramide (Gb3) in blood vessel walls throughout a person’s body. Fabry disease occurs in one person per 40,000.
PRX-102 is a plant cell culture-expressed, and a PEGylated, stable recombinant alpha-Galactosidase-A protein. In our clinical research, pegunigalsidase alfa appears to have a favorable circulatory half-life, with targeted enzyme activity in organs affected by Fabry disease.
Based on our clinical data to date, we believe that these characteristics may potentially enable a treatment option of once-monthly infusions in addition to bi-weekly infusions. We are developing pegunigalsidase alfa in two alternative doses and regimens with the goal of meeting two important, unmet needs: demonstrating benefit for Fabry patients with declining renal function; and lowering the treatment burden of bi-weekly infusions.
Alidornase alfa, or PRX-110 for the treatment of cystic fibrosis is our plant cell-expressed recombinant form of human deoxyribonuclease I (DNase I) to reduce the viscosity of sputum that accumulates in the lungs of cystic fibrosis patients. This accumulation in the lungs of CF patients exposes them to recurrent infections and compromises lung function. DNase I therapy, is generally recommended for CF patients to improve lung function and reduce exacerbations. We developed alidornase alfa by chemically modifying the enzyme forming an actin inhibition resistant DNase I as actin is present in high quantities in patients’ sputum interfering with DNAse activity. This novel treatment candidate may result in improved lung function and decreased incidence of recurrent infections in patients.
OPRX-106 for inflammatory bowel disease is our plant cell-expressed recombinant human tumor necrosis factor receptor for inhibiting TNF alpha, which modulates immune response given orally while the plant cells serve as a natural capsule. When administered orally and while passing through the digestive tract, the plant cells function as a natural delivery vehicle, having the unique attribute of a cellulose cell wall which makes them resistant to degradation, compared to proteins produced via mammalian cell expression. Through oral administration, OPRX-106 avoids the systemic exposure that occurs when TNF alpha inhibitors are administered by injection or intravenous infusion. Oral administration may potentially lead to a safer to use anti-TNF. OPRX 106 may also be less immunogenic which can potentially result in longer term efficacy.
What has been your clinical progress to date and what are your commercialization goals?
Despite the ongoing COVID-19 pandemic, we’ve made exceptional progress in our lead program, PRX-102, or pegunigalsidase alfa, for the treatment of Fabry disease. We believe we have one of the most comprehensive clinical programs currently underway for this important and underserved inherited disease.
We recently announced positive topline results from our BRIDGE Phase III open-label, switch-over clinical trial of PRX-102. The study met its main objectives for safety and efficacy, as well as indicated substantial improvement in renal function in patients switched from Replagal® to PRX-102, confirming our beliefs that PRX-102 can be an important enzyme replacement therapy for Fabry patients.
Our other two Phase III studies are ongoing and fully enrolled and consist of our BALANCE study, evaluating the safety and efficacy of pegunigalsidase alfa 1mg/kg dosed every 2 weeks and assessing its effects in Fabry patients with declining renal function versus the currently used enzyme replacement therapy, Fabrazyme®. And our BRIGHT study, evaluating the safety and efficacy of pegunigalsidase alfa 2mg/kg, dosed once every 4 weeks, and assessing whether patients maintain clinical stability after being switched to this regimen from currently used enzyme replacement therapies (Replagal and Fabrazyme®) dosed bi-weekly.
Together with our development and commercialization partner, Chiesi Farmaceutici S.p.A, we submitted a BLA to the U.S. FDA for PRX-102 through the FDA’s Accelerated Approval pathway. PRX-102 was also granted Fast Track designation by the FDA in January 2018. And we and Chiesi also received an Initial Pediatric Study Plan agreement letter from the FDA for PRX-102, outlining an agreed-upon approach to address the evaluation in pediatric Fabry patients.
There remains still, despite years of existing enzyme replacement therapies, an unmet medical need in Fabry patients who continue to show progressive disease progression. We believe an accelerated approval for PRX-102 will potentially bring a new treatment option that can bring hope for these patients, and that is the goal we at Protalix are all working towards.
About Protalix BioTherapeutics, Inc.
Protalix (NYSE American: PLX) is a biopharmaceutical company focused on the development and commercialization of recombinant therapeutic proteins expressed through its proprietary plant cell-based expression system, ProCellEx®. Protalix was the first company to gain U.S. Food and Drug Administration approval of a therapeutic protein produced by a plant cell-based expression system. Protalix’s unique expression system represents a new method for developing recombinant proteins in an industrial-scale manner. Their pipeline consists of proprietary, potentially clinically superior versions of recombinant therapeutic proteins that target established pharmaceutical markets.
About Dror Bashan, Protalix BioTherapeutics’ President and CEO
Dror Bashan joined Protalix BioTherapeutics as President and Chief Executive Officer, and as a director of the Company, in June 2019. He has over 20 years of experience in the pharmaceutical industry with roles ranging from business development, marketing, sales and finance providing him with both cross regional and cross discipline experience and a deep knowledge of the global pharmaceutical and health industries. From 1998 through 2018, he served in a number of senior positions at Teva Pharmaceutical Industries Ltd. Most recently, he served as Teva’s Senior Vice President, Global Business Development, and was involved in strategic alliances, cross-company strategic projects and the acquisition and divestiture of assets. Mr. Bashan holds a BA in Economics and Business Management from the Tel Aviv University and an MBA from the Tel-Aviv University.